Abstract Creep is the macroscopic manifestation of the process of generation, expansion, and penetration of microscopic cracks in a rock body. In this study, the GDEM continuous–discontinuous ...numerical simulation software was used to model a rock body containing X-fractured for the purposes of exploring creep crack expansion and rupture in the rock body, analyzing the effects of various factors on X-fractured the rock body under the rule of change of the creep curve, and assessing the influences of the intersection angle of the fracture and other factors on the non-parallel fractured rock body on the creep rupture process. The results show that an X-fractured rock body exhibits a mixed tensile–shear damage mode, with tensile damage being the main type of damage. In the isotropic creep stage of a rock body with X-fractured , the steady-state creep rate initially increases and then decreases as the sub- fracture length increases, with the change of the fracture angle of the creep rate of the w-type; the sub-fracture length of h is 14 mm, the rock body is the first to enter into the accelerated creep stage, for the different fracture intersection angle of the rock body For the rock mass with different fracture angles, the time sequence of entering the accelerated creep stage is consistent with the creep rate; when the fracture intersection angle is 45°, and the sub-fracture length is 12 mm, the rock mass has the largest degree of fragmentation, which has a significant impact on the creep damage; after using a single variable processing, it is found that the fracture intersection angle, the sub-fracture length and other factors compared to the fracture intersection angle has a greater impact on the creep damage of the X-fractured rock body. This paper can provide theoretical basis and reference for the study of rock engineering creep damage law and mechanical properties of X-fractured rock body.
Gut microbiota comprises the microbial communities inhabiting our gastrointestinal (GI) tracts. Accordingly, these complex communities play a fundamental role in many host processes and are closely ...implicated in human health and diseases. Sleep deprivation (SD) has become increasingly common in modern society, partly owing to the rising pressure of work and the diversification of entertainment. It is well documented that sleep loss is a significant cause of various adverse outcomes on human health including immune-related and metabolic diseases. Furthermore, accumulating evidence suggests that gut microbiota dysbiosis is associated with these SD-induced human diseases. In this review, we summarize the gut microbiota dysbiosis caused by SD and the succedent diseases ranging from the immune system and metabolic system to various organs and highlight the critical roles of gut microbiota in these diseases. The implications and possible strategies to alleviate SD-related human diseases are also provided.
Effluent dissolved organic nitrogen（DON） is problematic in nutrient sensitive surface waters and needs to be reduced to meet demanding total dissolved nitrogen discharge limits.Bioavailable ...DON（ABDON） is a portion of DON utilized by algae or algae ＋ bacteria,while biodegradable DON（BDON） is a portion of DON decomposable by bacteria.ABDON and BDON in a two-stage trickling filter（TF） wastewater treatment plant was evaluated using three different microalgal species,Selenastrum capricornutum,Chlamydomonas reinhardtii and Chlorella vulgaris and mixed cultured bacteria.Results showed that up to80% of DON was bioavailable to algae or algae ＋ bacteria inoculum while up to 60% of DON was biodegradable in all the samples.Results showed that C.reinhardtii and C.vulgaris can be used as a test species the same as S.capricornutum since there were no significant differences among these three algae species based on their ability to remove nitrogen species.
Increased attention has been paid to PM2.5 pollution in China. Due to its detrimental effects on environment and health, it is important to establish a PM2.5 concentration forecasting model with high ...precision for its monitoring and controlling. This paper presents a novel hybrid model based on principal component analysis (PCA) and least squares support vector machine (LSSVM) optimized by cuckoo search (CS). First PCA is adopted to extract original features and reduce dimension for input selection. Then LSSVM is applied to predict the daily PM2.5 concentration. The parameters in LSSVM are fine-tuned by CS to improve its generalization. An experiment study reveals that the proposed approach outperforms a single LSSVM model with default parameters and a general regression neural network (GRNN) model in PM2.5 concentration prediction. Therefore the established model presents the potential to be applied to air quality forecasting systems.
•PCA is adopted to extract original features and reduce dimension for input selection.•LSSVM model is firstly proposed for PM2.5 concentration prediction.•The novel hybrid model PCA-CS-LSSVM outperforms single LSSVM and GRNN models in terms of prediction precision.•The model presents strong potential to be applied to air quality forecasting systems.
Neural stem cells (NSCs), especially human NSCs, undergo cellular senescence characterized by an irreversible proliferation arrest and loss of stemness after prolonged culture. While compelling ...correlative data have been generated to support the oxidative stress theory as one of the primary determinants of cellular senescence of NSCs, a direct cause-and-effect relationship between the accumulation of oxidation-mediated damage and cellular senescence of NSCs has yet to be firmly established. Human SOD1 (hSOD1) is susceptible to oxidation. Once oxidized, it undergoes aberrant misfolding and gains toxic properties associated with age-related neurodegenerative disorders. The present study aims to examine the role of oxidized hSOD1 in the senescence of NSCs.
NSCs prepared from transgenic mice expressing the wild-type hSOD1 gene were maintained in culture through repeated passages. Extracellular vesicles (EVs) were isolated from culture media at each passage. To selectively knock down oxidized SOD1 in NSCs and EVs, we used a peptide-directed chaperone-mediated protein degradation system named CT4 that we developed recently.
In NSCs expressing the hSOD1 from passage 5, we detected a significant increase of oxidized hSOD1 and an increased expression of biomarkers of cellular senescence, including upregulation of P53 and SA-β-Gal and cytoplasmic translocation of HMGB1. The removal of oxidized SOD1 remarkably increased the proliferation and stemness of the NSCs. Meanwhile, EVs derived from senescent NSCs carrying the wild-type hSOD1 contained high levels of oxidized hSOD1, which could accelerate the senescence of young NSCs and induce the death of cultured neurons. The removal of oxidized hSOD1 from the EVs abolished their senescence-inducing activity. Blocking oxidized SOD1 on EVs with the SOD1 binding domain of the CT4 peptide mitigated its toxicity to neurons.
Oxidized hSOD1 is a causal factor in the cellular senescence of NSCs. The removal of oxidized hSOD1 is a strategy to rejuvenate NSCs and to improve the quality of EVs derived from senescent cells.
We present the first experimental demonstration of an integrated microwave photonic circuit for active, analog self-interference cancellation. The circuit is unique in its ability to operate in any ...radio frequency (RF) band from 400 MHz up to 6 GHz while not requiring any optical inputs or outputs. We focus on two topics related to the functional performance of the circuit. First, we investigate the amount of interference cancellation that can be achieved over a wide range of operating frequencies. We show that the circuit can achieve nearly -30 dB of interference cancellation across all existing frequency-division duplexed local thermal equilibrium and WiFi bands. Second, we investigate the control aspects of the integrated circuit and determine how much amplitude and phase tunability can be generated to perform active cancellation. Using dispersive techniques, the integrated circuit achieves 10 dB and 52° of independent amplitude and phase tunability, respectively, at 1.25 GHz. The range decreases with increasing frequency. We find that the sensitivity of the circuit's cancellation performance to the control biases are 2 and 0.5 mA at cancellation depths of -40 and -50 dB, respectively. Finally, we use the integrated circuit to demonstrate adaptive interference cancellation. Our results show that an integrated solution is able to achieve a cancellation performance comparable to a discrete fiber-optic system. Additionally, it is one of the first demonstrations of an integrated microwave photonic circuit that only possesses RF inputs and outputs.
Background
Severe traumatic brain injury (TBI) results in long‐term neurological deficits associated with white matter injury (WMI). Ethyl pyruvate (EP) is a simple derivative of the endogenous ...energy substrate pyruvate with neuroprotective properties, but its role in recovery from WMI has not been explored.
Aims
This study examines the effect of EP treatment on rats following TBI using behavioral tests and white matter histological analysis up to 28 days post‐injury.
Materials and Methods
Anaesthetised adult rats were subjected to TBI by controlled cortical impact. After surgery, EP or Ringers solution (RS) was administrated intraperitoneally at 15 min after TBI and again at 12, 24, 36, 48, and 60 h after TBI. Sensorimotor deficits were evaluated up to day 21 after TBI by four independent tests. Immunofluorescence and transmission electron microscopy (TEM) were performed to assess white matter injury. Microglia activation and related inflammatory molecules were examined up to day 14 after TBI by immunohistochemistry or real‐time PCR.
Results
Here, we demonstrate that EP improves sensorimotor function following TBI as well as improves white matter outcomes up to 28 d after TBI, as shown by reduced myelin loss. Furthermore, EP administration during the acute phase of TBI recovery shifted microglia polarization toward the anti‐inflammatoryM2 phenotype, modulating the release of inflammatory‐related factors.
Conclusion
EP treatment may protect TBI‐induced WMI via modulating microglia polarization toward M2.
Excessive glutamate in cerebrospinal fluid after subarachnoid hemorrhage (SAH) causes excitotoxic damage through calcium overloading and a subsequent apoptotic cascade. GluN1/GluN2B containing ...N-methyl-Daspartate (NMDA) receptor and metabotropic glutamate receptor 1 (mGluR1) can play a leading role in glutamate-mediated excitotoxicity. Here we report that Ifenprodil (100μM), a negative allosteric modulator (NAM) of GluN1/GluN2B NMDA receptors, and JNJ16259685 (10μM), a NAM of mGluR1, have an additive efficacy against glutamate (100μM)-induced Ca2+ release and cell apoptosis in primary cortical, hippocampal, and cerebellar granule neurons. Compared with intraperitoneal injection of Ifenprodil (10mg/kg) and JNJ16259685 (1mg/kg) separately, the combination therapy of Ifenprodil plus JNJ16259685 significantly improves the neurological deficit at 24h and 72h after experimental SAH. It reduces the number of TUNEL/DAPI-positive and activated caspase-3/NeuN-positive cells in cortical and hippocampal CA1 regions at 72h, decreases levels of glutamate in cerebrospinal fluid at 72h, and reduces the mitochondrial Ca2+ concentration. Meanwhile, the combination therapy attenuates apoptosis as shown by an increased Bcl-2 expression, decreased Bax expression and release of cytochrome c, and reduction of cleaved caspase-9 and caspase-3 at 24h after SAH. These findings indicate that targeting both the intracellular Ca2+ overloading and neuronal apoptosis using the Ifenprodil and JNJ16259685 is a promising new therapy for SAH.
Excessive glutamate causes over-stimulation of GluN1/GluN2B NMDA receptors and mGluR1, which in turn contributes to the calcium overload and cell death. Blockage of GluN1/GluN2B NMDA receptors and mGluR1 using combination therapy of Ifenprodil and JNJ16259685 has additive efficacy against SAH-induced neurological deficit and neuronal apoptosis. Display omitted
•Ifenprodil and JNJ16259685 have additive effect against glutamate-mediated Ca2+ overloading and cell apoptosis.•Ifenprodil and JNJ16259685 have enhanced neuroprotection against early brain injury after SAH.•A dual-target inhibition of Ca2+ overloading and apoptosis using the Ifenprodil and JNJ16259685
This paper focuses on multi-target parameter estimation of multiple-input multiple-output (MIMO) radar with widely separated antennas on moving platforms. Aiming at the superimposed signals caused by ...multi-targets, the well-known expectation maximization (EM) is used in this paper. Target’s radar cross-section (RCS) spatial variations, different path losses and spatially-non-white noise appear because of the widely separated antennas. These variables are collectively referred to as signal-to-noise ratio (SNR) fluctuations. To estimate the echo delay/Doppler shift and SNR, the Q function of EM algorithm is extended. In addition, to reduce the computational complexity of EM algorithm, the gradient descent is used in M-step of EM algorithm. The modified EM algorithm is called generalized adaptive EM (GAEM) algorithm. Then, a weighted iterative least squares (WILS) algorithm is used to jointly estimate the target positions and velocities based on the results of GAEM algorithm. This paper also derives the Cramér-Rao bound (CRB) in such a non-ideal environment. Finally, extensive numerical simulations are carried out to validate the effectiveness of the proposed algorithm.
Nowadays, both customers and producers prefer thin-tailed fat sheep. To effectively breed for this phenotype, it is important to identify candidate genes and uncover the genetic mechanism related to ...tail fat deposition in sheep. Accumulating evidence suggesting that post-transcriptional modification events of precursor-messenger RNA (pre-mRNA), including alternative splicing (AS) and alternative polyadenylation (APA), may regulate tail fat deposition in sheep. Differentially expressed transcripts (DETs) analysis is a way to identify candidate genes related to tail fat deposition. However, due to the technological limitation, post-transcriptional modification events in the tail fat of sheep and DETs between thin-tailed and fat-tailed sheep remains unclear.
In the present study, we applied pooled PacBio isoform sequencing (Iso-Seq) to generate transcriptomic data of tail fat tissue from six sheep (three thin-tailed sheep and three fat-tailed sheep). By comparing with reference genome, potential gene loci and novel transcripts were identified. Post-transcriptional modification events, including AS and APA, and lncRNA in sheep tail fat were uncovered using pooled Iso-Seq data. Combining Iso-Seq data with six RNA-sequencing (RNA-Seq) data, DETs between thin- and fat-tailed sheep were identified. Protein protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were implemented to investigate the potential functions of DETs.
In the present study, we revealed the transcriptomic complexity of the tail fat of sheep, result in 9,001 potential novel gene loci, 17,834 AS events, 5,791 APA events, and 3,764 lncRNAs. Combining Iso-Seq data with RNA-Seq data, we identified hundreds of DETs between thin- and fat-tailed sheep. Among them, 21 differentially expressed lncRNAs, such as ENSOART00020036299, ENSOART00020033641, ENSOART00020024562, ENSOART00020003848 and 9.53.1 may regulate tail fat deposition. Many novel transcripts were identified as DETs, including 15.527.13 (
), 13.624.23 (
), 11.689.28 (
), 11.689.18 (
), 11.689.14 (
), 11.660.12 (
), 22.289.6 (
), 22.289.3 (
) and 22.289.14 (
). Most of the identified DETs have been enriched in GO and KEGG pathways related to extracellular matrix (ECM). Our result revealed the transcriptome complexity and identified many candidate transcripts in tail fat, which could enhance the understanding of molecular mechanisms behind tail fat deposition.
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